The term avermectin (previously referred to as C-076) is used to describe a series of compounds isolated from the fermentation broth of an avermectin producing strain of Streptomyces avermitilis and derivatives thereof. The morphological characteristics of the culture are completely described in U.S. Pat. No. 4,310,519. The avermectin compounds are a series of macrolides, each of which is substituted thereon at the 13-position with a 4-(.alpha.-L-oleandrosyl)-.alpha.-L-oleandrose group. The avermectin compounds and the instant derivatives thereof have a very high degree of anthelmintic and anti-parasitic activity.
The avermectin series of compounds isolated from the fermentation broth have the following structures: ##STR1##
wherein R is the 4'-(.alpha.-1-oleandrosy)-.alpha.-1-oleandrose group of the structure: ##STR2## and wherein the broken line indicates a single or a double bond;
R.sub.1 is hydrogen or hydroxy and is present only when said broken line indicates a signal bond;
R.sub.2 is iso-propyl or sec-butyl; and
R.sub.3 is methoxy or hydroxy.
There are eight different avermectin natural product compounds and they are given the designations A1a, A1b, A2a, A2b, B1a, B1b, B2a and B2b based upon the structure of the individual compounds.
In the foregoing structural formula, the individual avermectin compounds are as set forth below. (The R group is 4'(.alpha.-L oleandrosyl)-.alpha.-L-oleandrose):
______________________________________ R.sub.1 R.sub.2 R.sub.3 ______________________________________ A1a (22,23-Double Bond) sec-butyl --OCH.sub.3 A1b (22,23-Double Bond) iso-propyl --OCH.sub.3 A2a --OH sec-butyl --OCH.sub.3 A2B --OH iso-propyl --OCH.sub.3 B1a (22,23-Double Bond) sec-butyl --OH B1b (22,23-Double Bond) iso-propyl --OH B2a --OH sec-butyl --OH B2b --OH iso-propyl --OH ______________________________________
The avermectin compounds are generally isolated as mixtures of a and b components. Such compounds differ only in the nature of the R.sub.2 substituent and the minor structural differences have been found to have very little effect on the isolation procedures, chemical reactivity and biological activity of such compounds.
The terminal hydroxy group of the 13-position disaccharide substituent is situated at what is referred to as the 4"-position. In U.S. Pat. No. 4,427,663 to Mrozik, certain 4" derivatives of avermectin compounds are discussed, specifically 4"-amino compounds. Amino and alkyl amino derivatives at the 4"-position are disclosed however the semicarbazones and hydrazones of the instant invention are not suggested.